Virulent M. tuberculosis induces life-long immunity against reinfection in individuals who develop the latent form of this disease. The resulting immunity is substantially better than that achieved in BCG vaccinated animals (and presumably, people). Virulent M. tb H37Rv was attenuated by a targeted mutagenesis of the leu and lys genes and the resulting auxotrophs were injected into mice and guinea pigs to assess their survival in the lung and spleen as a measure of their residual virulence and immunogenicity. The mice were challenged with a small aerogenic inoculum of M. tb Erdman 1-3 months later and the growth in the lungs was compared with that for the BCG controls.